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SRP041755
Homo sapiens
8 Downloadable Samples
IlluminaHiSeq2000
Description
Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. Although these cells line the media of the glomerular afferent arterioles and share some characteristics with contractile cells, they are filled with lysosome-like organelles where renin is activated and stored for regulated secretion in response to physiological and pathophysiological stimuli. Chronic stimulation of renin release results in a recruitment of new JG cells by the seeming conversion of adjacent smooth muscle cells along the afferent arterioles. Because JG cells rapidly de-differentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain largely unclear. In an effort to overcome this limitation, we have performed RNA expression analysis on four human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in mouse kidney. Our results add 40 new genes to the list that characterize renin-producing cells and reveal a significant variation in the expression patterns of developing, mature and recruited JG cells. Overall design: RNA-Seq was performed with a HiSeq 2000 on three biopsies of a first reninoma from Paris (Par1B1-B3), one biopsy from a reninoma from Montreal (Mon), two biopsies from a reninoma from Rotterdam (RotB1, B2), and a second reninoma from Paris (Par2) along with a biopsy from adjacent supposedly normal tissue from the same patient (Par2N).
Publication Title
Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
NLRC5 is a member of the NLR family of proteins. The observation that NLRC5 is found in the nucleus prompted us to perform a gene array to identify putative target genes of NLRC5. We generated Jurkat T cell lines that stably express either the wild-type or mutant forms of NLRC5 harboring mutations in the nucleotide binding domain (NBD): Walker A (deficient in nucleotide binding), Walker B (deficient in nucleotide hydrolysis), and the combined Walker AB, carrying both mutations.
Publication Title
NLR family member NLRC5 is a transcriptional regulator of MHC class I genes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The results of this study indicate that stenotic fibroblasts exhibit an aberrant response to tissue stiffness with reduced MMP activity, leading to a perpetuous vicious circle of ever more fibrosis formation. Altering the microenvironment by LOX inhibition increases MMP activity and decreases ECM contraction, resulting in a potential anti-fibrotic agent for Crohns disease.
Publication Title
Fibrostenotic Phenotype of Myofibroblasts in Crohn's Disease is Dependent on Tissue Stiffness and Reversed by LOX Inhibition.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The peroxisome proliferator-activated receptor alpha (PPAR) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPAR in the small intestine. Since this organ is frequently exposed to high levels of PPAR ligands via the diet, we set out to characterize the function of PPAR in small intestine using functional genomics experiments and bioinformatics tools. PPAR was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPAR was expressed highest in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPAR activation. Additional analyses showed that intestinal PPAR dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height, and a 34% increase in villus area of wild-type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPAR in the small intestine. We show that PPAR is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases.
Publication Title
Genome-wide analysis of PPARalpha activation in murine small intestine.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Gene expression regulation of transporters and phase I/II metabolic enzymes in murine small intestine during fasting
Publication Title
Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Crossing of hDMD mice that contain the full-length 2.3 Mb hDMD gene were crossed with dystrophin-deficient mdx mice and dystrophin and utrophin double-deficient mdx x utrn-/- mice resulted in a full rescue of the dystrophic features of these mice, as concluded from histological analysis. Analysis on Affymetrix gene chips demonstrated that also expression profiles of the dystrophic mice were normalized by crossing with transgenic hDMD mice. This confirms the full functionality of the hDMD transgene in mice.
Publication Title
Generation and characterization of transgenic mice with the full-length human DMD gene.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we have compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Among these CD4+ T cell subsets, we detected differential expression of 421 proteins and 640 mRNAs, with only 48 molecules shared. Fifty proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFkB-, PI3 kinase/mTOR-, NFAT- and STAT pathways and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFkB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, while transitional FOXP3+ cells can. Our collective data reveal that Tregs protect their identity by a unique “wiring” of signalling pathways Overall design: mRNA profiles of 5 CD4+ T cell populations were generated by deep sequencing, in triplicate
Publication Title
Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Sp1 and Sp3 belong to the Specificity proteins (Sp)/Krüppel-like transcription factor family. They are closely related, ubiquitously expressed and recognize G-rich DNA motifs. They are thought to regulate generic processes such as cell cycle and growth control, metabolic pathways and apoptosis. Ablation of Sp1 or Sp3 in mice is lethal, and combined haploinsufficiency results in hematopoietic defects during the fetal stages. Here, we show that in adult mice conditional ablation of either Sp1 or Sp3 has minimal impact on hematopoiesis, while the simultaneous loss of Sp1 and Sp3 results in severe macrothrombocytopenia and platelet dysfunction. We employed flow cytometry, cell culture and electron microscopy and show that although megakaryocyte numbers are normal in bone marrow and spleen, they display a less compact demarcation membrane system and a striking inability to form proplatelets. Through megakaryocyte transcriptomics and platelet proteomics we identified several cytoskeleton-related proteins and downstream effector kinases, including Mylk, that were downregulated upon Sp1/Sp3 depletion, providing an explanation for the observed defects in megakaryopoiesis. We show that Mylk is required for proplatelet formation and stabilization and for ITAM-receptor mediated platelet aggregation. Our data highlights the specific vs generic role of these ubiquitous transcription factors in the highly specialized megakaryocytic lineage. Overall design: Megakaryocyte mRNA profiles of Sp1fl/fl::Sp3fl/fl (WTlox) and Pf4-Cre::Sp1fl/fl::Sp3fl/fl (dKO) mice were generated by deep sequencing, in triplicate.
Publication Title
Sp1/Sp3 transcription factors regulate hallmarks of megakaryocyte maturation and platelet formation and function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 155 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. A 40-gene CHEK2 signature was defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.
Publication Title
Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes.
Sample Metadata Fields
Specimen part
View Samples